In vivo and in vitro studies will evaluate the reproductive and fertility effects of two ubiquitous environmental contaminants, PCBs and DDE, on mammalian reproduction. Although use of these compounds were banned during the 1970's in the U.S., at present tissue levels of these two organochlorines in human and wildlife samples appear to have reached steady state. Transference of these compounds in utero across the placenta via the blood and from breast-feeding make the elimination of these exposure to new generations very unlikely in the short term. PCBs and DDE have been well studied individually, but little work has been done on possible synergistic effects on reproduction of these contaminants at environmentally-relevant levels of exposure. The present multigenerational investigation will utilize the native rodent Peromyscus polionotus as a model of assessment of risk to human as well as wildlife populations. Mated pairs will be exposured through the diet at the environmentally-relevant level of 5ppm PCBs (Aroclor 1254) and 5 ppm p,p' DDE individually in two groups of mice, while a third group will receive both contaminants. A control group will receive the same diet without PCBs or DDE. Offspring from the first generation of exposure will be paired with animals from the same regime to observe effects of two generations of exposure. Reproductive and fertility parameters including litter size, birth weight, survival to weaning and weaning weight will be measured in each of the two generations of mice investigated. Cell culture toxicity studies will determine if reproductive depression is due to direct toxic effects of PCBs or individual congeners on mammalian cells.